In a surgical setting, when a medical device is used, a risk of infection is created. The risk of infection dramatically increases for invasive or implantable medical devices, such as intravenous catheters, arterial grafts, intrathecal or intracerebral shunts and prosthetic devices, which create a portal of entry for pathogens while in intimate contact with body tissues and fluids. The occurrence of surgical site infections is often associated with bacteria that colonize on the medical device. For example, during a surgical procedure, bacteria from the surrounding atmosphere may enter the surgical site and attach to the medical device. Bacteria can use the implanted medical device as a pathway to surrounding tissue. Such bacterial colonization on the medical device may lead to infection and morbidity and mortality to the patient.
A number of methods for reducing the risk of infection associated with invasive or implantable medical devices have been developed that incorporate antimicrobial agents into the medical devices. Such devices desirably provide effective levels of antimicrobial agent while the device is being used.
Amidoamines are best known as surface-active agents. They are also known for their ability to serve as core initiators for dendrimer synthesis and for assembly of poly(amidoamine) dendrimers. Amidoamines in their monomeric form can serve as binders or crosslinking reagents that provide reactive groups for attaching biomolecules or other compounds together or to material surfaces.
Amidoamines have been used with silicone polymers for cosmetic or hair conditioning applications. For example, U.S. Pat. No. 5,166,297 proposes a dimethicone copolyol halo ester intermediate which is said to be useful as an intermediate for reaction with amines to prepare silicone based quaternary compounds for cosmetic or hair conditioning applications.
U.S. Pat. No. 5,237,035 proposes silicone phospholipid polymers which are highly lubricious, produce high levels of foam, have low irritation properties and are film formers when applied to hair and skin. The compounds, because they are based upon terminal dimethicone copoylols make flat polymers when phosphated and derivatized. The polymers are said to orientate themselves into planar sheets, silicone on one side of the plane, a fatty portion on the other side in aqueous and other solutions. These flat polymers produce non-occlusive films when applied to hair skin and fiber.
U.S. Pat. No. 5,328,685 proposes a method of imparting improved conditioning properties to hair comprising treating the hair with a clear conditioning composition comprising an amidoamine salt, the amidoamine salt comprising an amidoamine compound and a silicone compound having at least one quaternary ammonium moiety.
Monomeric amidoamines, in particular myristamidopropyl dimethylamine (MAPD), are also known to have significant antifungal and antiamoebal activity. MAPD is a cationic oil-in-water emulsifier which is often used as a conditioner or a thickener. MAPD is currently used in ophthalmic compositions as a disinfecting and as a contact lens washing solution agent, preservative and surface active agent. In this regard, U.S. Pat. No. 5,393,491 proposes the use of certain amidoamines for disinfecting and cleaning contact lenses and preserving ophthalmic products, and associated ophthalmic compositions are described. U.S. Pat. Nos. 5,573,726 and 5,631,005 each also propose the use of certain amidoamines to disinfect contact lenses and preserve ophthalmic compositions. Ophthalmic compositions containing such compounds are also proposed. The amidoamines proposed are said to possess potent antibacterial and antifungal activity and are chemically compatible with inorganic ions and other materials utilized in ophthalmic compositions.
U.S. Pat. No. 6,617,142 proposes methods for forming a coating of an immobilized biomolecule on a surface of a medical device to impart improved biocompatibility for contacting tissue and bodily fluids. A biomolecule such as a glycoprotein having an unsubstituted amide moiety is proposed for combination with an amine forming agent to form an amine-functional biomolecule. The amine-functional biomolecule is combined with a medical device surface having a chemical moiety such as aldehyde, epoxide, isocyanate, 1,2-dicarbonyl, phosphate, sulfate or carboxylate to form a chemical bond immobilizing the biomolecule on the surface. The chemical bond may be combined with a reducing agent or a stabilizing agent. The aldehyde moiety may be formed by combining a periodate with a 2-aminoalcohol moiety or a 1,2-dihydroxy moiety. Also proposed is an amine-functional medical device surface combined with a biomolecule having a chemical moiety that reacts with an amine moiety. In one form, the amine-functional biomolecule is converted to a guanidino-functional biomolecule and is combined with a medical device surface having a chemical moiety that reacts with a guanidino moiety. In another form, the amine-functional medical device surface is converted to a guanidino-functional surface and is combined with a biomolecule having the chemical moiety.
The general use of amidoamines in treating or preventing infections caused by fungi or acanthamoeba is proposed in U.S. Patent Publication No. 2004/0058924. The amidoamines are said to be highly effective against both acanthamoeba and fungi and less toxic to delicate tissues that may become infected with these types of microorganisms, such as the cornea.
U.S. Patent Publication No. 2004/0033208 proposes antimicrobial compositions containing one or more topically active antibiotics, such as natamycin, and one or more amidoamines. The amidoamines are said to enhance or supplement the antimicrobial activity of natamycin or other topically active antibiotics. The compositions are said to be useful in treating or preventing fungal infections of the eye, ear, nose and throat, as well as sterilizing those tissues prior to surgery or other medical procedures.
WO9850087 proposes coated medical devices adapted to pass through narrow body openings such as catheters. The coatings provided impart durability to the catheter without appreciably adding to the thickness of the catheter and without decreasing the hoop tensile strength of the catheter. The use of amidoamine (EpiCure 3005) to prepare polymeric coatings with an epoxy resin is also proposed.
WO0126708 proposes polymeric valves, valve devices, machines and instruments. The proposed devices include implantable devices with a sufficiently long lifetime that are responsive to the patient's therapeutic requirements and deliver a certain amount of a drug in response to a biological stimulus. Also proposed are methods and processes using a reservoir implant with a valve, whereby a polymeric dendrimeric poly(amidoamine) could be placed into a gel.
Despite these advances in the art, it would be beneficial to incorporate an antimicrobial cationic surfactant into an invasive or implantable medical device to reduce the risk of infection. Further, it would be desirable to provide an antimicrobial composition where the release mechanism into the target environment is independent of the solubilization of the antimicrobial composition in the target environment, and that exhibits immediate activity upon contact with fluids in the human body.